PROJECT SUMMARY/ABSTRACT Nearly 60% of youths in the U.S. are exposed to childhood adversity, including violence exposure, abuse, neglect, loss of caregivers, and living in poverty. Global and national data indicate that adversity accounts for 30-50% of the risk for depression onset from childhood through adolescence, and response to evidence-based front-line interventions (e.g., cognitive behavioral therapy [CBT] and antidepressants) is notably poor among adversity-exposed youths. Research demonstrates that exposure to adversity disrupts general learning processes, including higher-order cognitive processes (i.e., cognitive control). Learning impairments may impede one of the most common and critical intermediary treatment processes across evidence-based psychotherapies: the acquisition of therapy skills. This proposal uses an innovative approach to investigate childhood adversity exposure as a predictor of skill acquisition for the most commonly implemented CBT skill with depressed youths, cognitive restructuring. To refine interventions and optimize effectiveness, it is critical to identify how existing treatments break down. This study will use a repeated-measures, multiple levels of analysis approach to assess acquisition and retention of an experimenter-introduced cognitive restructuring skill, among depressed adolescents with population-level variability in lifetime adversity exposure (n=90). The candidate proposes to investigate associations between adversity exposure and learning-related cognitive control processes in the context of adolescent depression (Aim 1). Adversity exposure and cognitive control will be examined as direct predictors of CBT skill acquisition and skill retention over six-months; an indirect pathway from adversity to skill acquisition through cognitive control will also be examined (Aim 2). The candidate will further explore key characteristics of adversity, namely the type (threat of harm versus deprivation of resources) and developmental timing of exposure, as distinct predictors of skill acquisition (exploratory Aim 3). The proposed K23 builds on the candidate?s prior training in environmental and biobehavioral risk for psychopathology, and evaluation of treatment effectiveness, with new training in 1) experimental therapeutics; 2) developmental conceptualizations of childhood adversity, and 3) behavioral assessments of cognitive and affective learning processes. The Department of Psychiatry at the University of Pittsburgh is an ideal scientific setting to achieve the proposed career development goals, and the candidate will receive training from a team of mentors (Drs. Goldstein, Luby, and Sheridan) and consultants (Drs. Forbes, Lindhiem, and Wallace) with expertise in target-focused intervention research, child adversity and risk for poor clinical course in youth depression, and developmental cognitive and affective science. The near-term goal of this award is to identify sensitive markers of depression intervention response among adversity-exposed youths. This will provide a crucial vehicle to advance the candidate?s overarching career objective: to develop a translational research program leveraging advances in basic science to inform experimental therapeutics for personalizing and optimizing depression treatment in high-risk youths.